Hydroxylation of unsaturated carboxylic acid compounds and the like



or the group Patented June 25, 1946 UNITED sTAT s PATENT orrlcs HYDBOXYLATION OF UNSATCRATED CAR- I BOXYLIC ACID COMPOUNDS AND THE LIKE Nicholas A. Milas, Belmont, Masa, assignor t Research CorporatiomNew York, N. Y., a corporatipn of New York N Drawing. Application March 16, 1942, 7

Serial No. 434,982

6 Claims. (Cl. 260-406) sideration of the following description wherein I have illustrated the application of my new proces in the preparation of various substances constituting the class of oxygenated organic com- Pounds.

The invention, whichis a continuation-in-part of my application Serial No. 382,273,'flled March '7, 1941, is concerned with the hydroxylation of unsaturated aliphatic compounds containing oleyields of ethyl dihydroxybutyrate from ethyl crotonate, diethyl mesotartrate from diethyl maleate, diethyl racemate from diethyl iumarate, 2-methyl-pentane-diol-2,3-one-4 from mesityl oxide, glycolaldehyde from vinyl acetate, glycolaldehyde from divinyl ether, glycolaldehyde from vinyl bromide, 9,1G-dihydroxy-stearic acid from oleic acid, p-phenylglyoerol and di( B'-phenylglycerol) ether from cinnamyl alcohol, glycerol from allyl alcohol, phenyl glyceric acid from cinnamic acid, dihydroxybutyric acid from crotonic acid, mesotartaric acid from maleic acid, racemic acid from fumaric acid, anisaldehyde and anisic acid finic or acetylenic linkages and composed of carbon, hydrogen and oxygen atoms only. This invention is more particularly concerned with the hydroxylation' of unsaturated aliphatic com- P n s ont ining oleflnic or acetylenic linkages and either the group that is to say, carboxylic acid compounds, aldehydes, ketones, alcohols, or ethers of such unsaturated compounds.

I have found that when an unsaturated organic compound of the type above described is treated ,mium tetroxide, ruthenium tetroxide, vanadium pentoxide, molybdenum oxide or chromium trioxide, in an essentially non-alkaline environment (that is, in the absence of an inorganic base), there is produced an oxygenated organic com- .pound, the nature of which depends upon the particular type of unsaturated compound subjected to such treatment, the temperature, the pressure (it the compound treated b in gaseous phase), the solvent medium, the extent of oxidation and other such factors.

I have successfully produced substantially good from anethol, vanillln from isoeugenol, piperonal from isosairole, homopiperonal from safrole, dihydroxy-stearic acid from oleic acid, etc.

In carrying out my process successfully, it is advisable to employ substantially anhydrous solvents, preferably selected from such organic substances that do not undergo oxidation during the reaction. Tertiary alcohols in general, and particularly tertiary butyl and tertiary amyl alcohols, have been found to be suitable solvents for this purpose, although it is to be understood that the invention is not confined to these solvents since various other reagents, such as nitriles and certain types of ethers, acetic acid-tertiary alcohol mixtures, etc., may be used to advantage. Iilustrative of operable nitriles is acetonitrile. Illustrative examples of operable ethers include: ethyl, propyl, butyl and amyl dioxane, ethers oi ethylene glycol and diethylene glycol, etc. Among operable inert (that is, unreactive) organic solvent media is nitromethane. The organic solvent employed is, in all cases, strictly a medium or vehicle, and is not a reactant.

The reaction mixture (material to be oxidized, the hydrogen peroxide treating agent, the organic solvent medium, where used, and the catalyst) preferably is initially substantially anhydrous.

A preferred procedure for the preparation of the hydrogen peroxide reagent in tertiary butyl alcohol is as follows:

400 cc. 01' pure tertiary butyl alcohol is added to cc. of 30% hydrogen peroxide (Albone C), and the solution treated with small portions of anhydrous sodium sulphate, thereby forming two layers. The alcohol layer, containing most of the hydrogen peroxide, is removed. The so sep-' arated hydrogen peroxide-rich layer may be used without further treatment; however, I may further dehydrate the same by treating it with more anhydrous sodium sulphate, and finally with anhydrous calcium sulphate or magnesium sulphate.

3 A solution containing approximately 6% hyrogen peroxide in tertiary butyl alcohol is thus obtained, and. this solution may be concentrated by vacuum distillation of the alcohol at room temperatureto any desired concentration without loss of the peroxide, provided an all-glass or other suitable apparatus is employed.

An osmium tetroxide catalyst may be prepared by dissolving substantially anhydrous osmium tetroxide in substantially pure tertiary butyl alcohol, free from isobutylene.

A chromium trioxide catalyst similarly may be prepared by dissolving substantially anhydrous chromic acid (CrOa) in a substantially pure saturated tertiary aliphatic alcohol (CnH2n+1)3CoH, e. g., substantially pure tertiary butyl or amyl alcohol, or in a substantially anhydrous mixture of acetic acid and a tertiary alcohol; or, the substantially anhydrous CrOa may be added directly in the solid form to the substantially anhydrous medium containing hydrogen peroxide and the substance to be hydroxylated Preparation of the other catalytic metal oxides may similarly be formed by dissolving the metal oxide in one or another of the organic solvents above stated. Or, the selected catalytic metal oxids may be added, in powdered or finely divided state, to the hydrogen peroxide reagent wherein the, same eventually dissolves forming a completely homogeneous solution. The catalyst may be used alone or in combination.

I have found that the temperature plays an important role in directing the type of oxygenated product to be formed. For example, formation of glycols in high yields is usually favored between room temperature (e. g., 21 C.) and several degrees below 0 0., whereas aldehydes, ketones and organic acids are produced more advantageously at temperatures higher than room temperature (e. g., between 21 C. and the boiling point of the non-aqueous solvent employed).

The following examples are illustrative of the application of the invention:

1. Gaseous Unssrunsran SUBSTANCE For the production of ethylene glycol or of any lycol fromanylunsaturated gaseous substance, the latter may be bubbled through the peroxide reagent containing any one of the catalysts above action is usually indicated by a color change or by the complete utilization of the peroxide as determined by titration. The glycol or other products may be separated by fractionation or in any other suitable manner.

2. Lmom m Soup UNSATURATED Suns-muons (a) Hzlclrocarl ony The unsaturated hydrocarbons are dissolved or mixed with the peroxide reagent containing a suitable catalyst of the type previously suggested and the reaction is allowed to proceed either at or belowroom temperature ii glycols are desired, or above room temperatur it aldehydes, ketones and organic acids are desired. The hydrocarbons may be present preferably in the ratio of one mole to one or two moles of the peroxide, although greater excess of peroxide is necessary when aldehydes, ketones and acids are desired. The speed of the reaction up to certain limits depends upon the concentration of the catalyst which may be present-preferably in concentrations from .05 g. to .5 g. per mole of the substance to be oxidized, although it is to be. understood.

Using the same procedure as in the foregoing examples, I have produced glycerol from allyl alcohol; 54% of ap-di-hydroxy butyric acid from crotonic acid; 56% of phenyl glyceric acid from cinnamic acid; 48% of racemic acid from fumaric acid; over 30% mesotartaric acid from maleic acid; 60% 9,10-dihydroxy stearic acid from oleic acid; 57% of diethyl racemate from diethyl fumarate; 55% of anisaldehyde from anethol; 66% of vanillin from isoeugenol; 68% yield of piperonal from isosairole; and 44% o! homopiperonal from safrole. In the case of some essential oils in which the double bonds are very active, the oxidation is apt to go beyond the glycol state, although it may be controlled to produce the glycol.

The invention is more particularly described and ifurther illustrated in the following:

Mesotantaric acid from maleic acid-To 2.9 g. (0.025 mole) of maleic acid were added 27.2 cc.

(0.05 mole) of 6.3% solution of hydrogen peroxide in anhydrous tertiary butyl alcohol and 2 cc. osmium tetroxide solution in tertiary butyl alcohol, and the mixture wasallowed to'stand overnight at room temperature. The reaction was complete on the following day when the solvent was removed under reduced pressure and the residue dissolved in water. The solution was then made ammoniacal, heated to boiling and treated with excess 10% calcium chloride solution, whereby the calcium oxalate and mesotartrate precipitated out. This precipitate was removed, dried and weighed: yield 1.9 g. To remove the calcium mesotartrate, the precipitate was extracted with 20% sodium hydroxide solution. This separation yielded 1.2 g. of calcium mesotartrate and 0.7 g. of calcium oxalate. The calcium mesotartrate was further purified by precipitation and analyzed.

The yield of mesotartaric acid was 30.3%, and that of oxalic acid 14.6%, of the 1.9 g. of maleic acid consumed in the reaction.

Vanillin from isoeuoenoL-Five grams 0: isoeugenol was mixed with 45 cc. 016.3% solution of hydrogen peroxide in anhydrous tertiary amyl alcohol and 0.02 g. of vanadium pentoxlde. The

. catalyst went into solution, which heated up spontaneously. The reaction was complete in about twelve hours when the mixture had become more intensely red. An analysis for the presence of vanillin by precipitating the p-nitrophenylhydrazone gave a yield of 66% of vanillin,

Anisaldehyde from anethole.-To 5 g. of anethole were added 45 cc. 01. 6.3% solution of hydrogen peroxide in anhydrous tertiary amyl alcohol and 0.02 g. oi! vanadium pentoxide. The

catalyst went slowly into solution, which heated up almost to the boiling point of the solvent. The reaction was over in about two hours when the mixture became deep red and the peroxide had completely disappeared. Considerable amounts of acetaldehyde vapor came oil during the reaction. The solvent was then removed under reduced pressure and the residue dissolved in 5 glacial acetic acid. Aliquot parts 01 this were analyzed for anisaldehyde. The yield of anisaldehyde amounted to 55%. Inaddition to anisaldehyde some anisic acid was isolated from the reaction, and a small amount of a deep red solid which is presumably an addition product of vanadium pentoxide with anisaldehyde.

Glycolaldehyde from vinyl acetate.To 17.7 g. of vinyl acetate (B. P. 72.5-73") was added 110 cc. 6.23% solution of hydrogen peroxide in tertiary butyl alcohol; the mixture was cooled to 0, and to it was added 1 cc. of a solution of osmium tetroxide in tertiary butyl alcohol. After five days at 0 the reaction was complete (reaction mixture turned brown, and peroxide had completely disappeared) whereupon the reaction mixture was distilled to remove unconverted vinyl acetate and the solvent. There was obtained a with 14.3 cc. of a 5.95% solution 01 hydrogen peroxide in tertiary butyl alcohol; the mixture was cooled to 0, and to it was added 0.5 cc. of

a solution of osmium tetroxide in tertiary butyl alcohol. The solution became orange in color, but after standing over night at 0 it turned colorless and the reaction was complete. A considerable amount of 9,10-dihydroxystearic acid had precipitated. The solventwas removed under reduced pressure and the residue was washed thoroughly with ether to remove any unconverted oleic acid. The washed, solid, product was recrystallized irom absolute alcohol; M. P. 129-131" (corn) Its neutralization equivalent was found to be 319. The yield amounted to 60%.

A further illustration of the invention is the application of the present process to the hydroxylation o! ricinoleic acid. When 1 mol of the latter starting material is refluxed with an amount of the peroxide reagent (containing vanadium pentoxide as catalyst) corresponding to 1 mol of hydrogen peroxide, the oleflnic linkage is disrupted with addition of one hydroxyl group toeach one of the two carbon atoms 01 the original oleflnic linkages, thus:

HO OH li -B1 c H in 5H t This latter productis adapted to be dehydrated, by known methods, to a compound containing a t io system of conjugated double bonds, thus:

Ethyl dlhydrozybutyrate from ethyl crotonate.A mixture of equimolecular quantities of ethyl erotonate and the peroxide reagent (with 'osmium tetroxide as catalyst), maintained at 0 C. for some time. produces ethyl dihydroxy- .butyrate.

alcohol was added to it, and the mixture allowed to warm up to room temperature. The reaction was complete after one day. An additional 25 cc. of the peroxide solution and 0.5 cc. of the 5 catalyst were then added, and the reaction mixture allowed to stand for one more day. Thereupon, the t-butyl alcohol was removed from the reaction mixture under reduced pressure, and the residue was separated into a crystallized solid (25%) and a highly viscous liquid. Four products were isolated from the solid product. Three of these were 9, 10, 12, 13-tetrahydroxystearic acids melting M1272 151-154" and mil-172 respectively. A fourth crystalline product melting at 109.5 was also isolated but its identity has not been definitely established.

The largest portion or the hydroxylated product was a viscous oil which could not be crystallized. After. several purifications by the precipitation method it was found to have a neutralization equivalent or about 238 and a Zerewitinofl number of about 2.6 showing that the product was not entirely pure, It was completely saturated to bromine in carbon tetrachloride. From all indications this product is a cleavage product of sativic acid (1. e., 01 9, 10, 12, 13-tetrahy- 'droxy stearic acid).

application Serial No. 136.600, through intervening application Serial No. 382,273. r

I claim:

1. Process of producing polyhydrox derivatives of such unsaturated organic-compounds as contain an olefinlc group and the group which comprises treating such unsaturated organic compound with a substantially anhydrous solution of hydrogen peroxide in an inert organic solvent medium and in the presence of a catalytically active oxide of a metal which forms unstable peracids, and recovering a polyhydroxy derivative of .the unsaturated organic compoun from the resulting reaction mixture.

2. Process defined in claim 1, in which the treatment is carried out at a temperature between normal room temperature and several degrees below 0 C.

3. Process of producing a polyhydroxy derivative of an unsaturated organic carboxylic acid compound, which comprises treating the compound with a substantially anhydrous solution of hydrogen peroxide in an inert organic solvent medium and in the presence of a catalytically active metal oxide of the group consisting of osmium tetroxide, ruthenium tetroxide, vanadium pentoxide, chromium trioxide and molybdenum oxide, at a temperature between normal room temperature and several degrees below 0 C.. and recovering a polyhydroxy derivative of the unsaturated organic carboxylic acid compound from the resulting reaction mixture.

4. Process of producing 9.10-dihydroxy stearic acid, which comprisestreating oleic acid, at a temperature below normal room temperature, with a substantially anhydrous solution of hydrogen peroxide in an inert'organic solvent medium and in the presence of a catalytically active oxide of metal which forms unstable, per and covering 9,10-dihydroxy stearic acid from the resulting reaction mixture. 1

5. Process of producing diethyl racemate, which comprises treating diethyl iumarate, at a 7 temperature. below normal room temperature,

This application is a continuation-in-part of onaco with a. substantially anhydrous solution of hydrogen peroxide in an inert organic Solvent medium and in the presence 01 a catalytlcs-lly active oxide of a metal which forms unstable peracids, and recovering diethyl racemate 1mm the resulting reaction mixture.

6. Process of producing z-methyl pentenediol- 2,3-0ne-4. which comprises treating meeltyl oz,-

perature, with a. substantially anhydrous solution of hydrogen peroxide in an inert organic solvent medium and in the presence of a. catalytically active oxide of a metal which forms unstable peracids, and recovering 2-methyl-pentane-diol- 2,3-one-4 from the resulting reaction mixture;

NICHOLAS A Mil-AS. 

